J Infect Chemother xxx (2017) 1e6

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Original Article

Transfer of vaginal chloramphenicol to circulating blood in pregnant

women and its relationship with their maternal background and
neonatal health
Satoe Harauchi a, Takashi Osawa a, Naoko Kubono a, Hiroaki Itoh b, Takafumi Naito a, *,
Junichi Kawakami a
a
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
b
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Few clinical studies have determined the quantitative transfer of vaginal chloramphenicol to circulating
Received 16 January 2017 blood in pregnant women. This study aimed to evaluate the plasma concentration of chloramphenicol in
Received in revised form pregnant women treated with trans-vaginal tablets and its relationship with maternal background and
1 March 2017
neonatal health. Thirty-seven pregnant women treated with 100 mg of trans-vaginal chloramphenicol
Accepted 28 March 2017
once daily for bacterial vaginosis and its suspected case were enrolled. The plasma concentration of
Available online xxx
chloramphenicol was determined using liquid chromatography coupled to tandem mass spectrometry at
day 2 or later after starting the medication. The correlations between the maternal plasma concentration
Keywords:
Chloramphenicol
of chloramphenicol and the background and neonatal health at birth were investigated. Chloramphenicol
Bacterial vaginosis was detected from all maternal plasma specimens and its concentration ranged from 0.043 to 73.1 ng/
Plasma concentration mL. The plasma concentration of chloramphenicol declined significantly with the administration period.
Pregnancy The plasma concentration of chloramphenicol was lower at the second than the first blood sampling. No
Trans-vaginal antibiotics correlations were observed between the maternal plasma concentration of chloramphenicol and back-
Neonatal infant ground such as number of previous births, gestational age at dosing, and clinical laboratory data.
Neonatal infant health parameters such as birth-weight, Apgar score at birth, and gestational age at the
time of childbearing were not related to the maternal plasma concentration of chloramphenicol. Vaginal
chloramphenicol transfers to circulating blood in pregnant women. The maternal plasma concentration
of chloramphenicol varied markedly and was associated with the administration day, but not with
maternal background or her neonatal health.
© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
Published by Elsevier Ltd. All rights reserved.

1. Introduction
Chloramphenicol is an antibiotic widely used to treat the bac-
terial infections caused by gram-negative coccoid bacterium, bacilli,
rickettsia, mycoplasma, and chlamydia. In Japan, trans-vaginal
chloramphenicol is used to treat the bacterial vaginosis [1]. Bacte-
rial vaginosis is a disease in which the normal vaginal flora is
Abbreviations: IQR, interquartile range; LCeMS/MS, liquid chromatography
coupled to tandem mass spectrometry; HPLCeUV, high performance liquid
chromatography coupled to ultraviolet detection.
* Corresponding author. Department of Hospital Pharmacy, Hamamatsu University
School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192,
Japan. Fax: þ81 53 435 2764.
E-mail address: naitou@hama-med.ac.jp (T. Naito).
replaced by anaerobic bacteria [2], and is the most common vaginal
infection in both pregnant and non-pregnant women [3]. The
compositions of vaginal microbiome differ between non-pregnant
women and pregnant women, and the prevalence of bacterial
vaginosis ranges from 10 to 20% in pregnant women [4e6]. Ac-
cording to the drug package insert of vaginal tablets containing
chloramphenicol, the drug does not transfer to circulating blood
[7]. Vaginal tablets containing chloramphenicol or metronidazole
are widely used to treat bacterial vaginosis in pregnant women in
Japan. In pregnant women, chloramphenicol as secondary choice
easily passes through placenta, and therefore may have an effect on
neonatal infants [8].
Chloramphenicol causes several serious adverse effects
including aplastic anemia, bone marrow suppression, and leukemia

http://dx.doi.org/10.1016/j.jiac.2017.03.015
1341-321X/© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Harauchi S, et al., Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its
relationship with their maternal background and neonatal health, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.03.015
2 S. Harauchi et al. / J Infect Chemother xxx (2017) 1e6
in adults. Gray baby syndrome is a known adverse effect of chlor-
amphenicol in neonatal infants [9,10]. Chloramphenicol is metab-
olized by uridine 50 -diphospho-glucuronosyltransferases in the
liver and converted to the glucuronate conjugate. Gray baby syn-
drome is a result of the inability to conjugate glucuronate by
neonatal infants, especially immature babies. The occurrence of
gray baby syndrome is potentially associated with the plasma
concentration of chloramphenicol in pregnant women [11]. The
effect of chloramphenicol on neonatal infants is an issue that must
be addressed when administering trans-vaginal chloramphenicol
to pregnant women.
Trans-vaginal chloramphenicol was not transferred into the
general circulation in an earlier observation [7]. In this earlier
observation, 34 women including 10 pregnant women who were
treated with 100 mg of trans-vaginal chloramphenicol were inves-
tigated. The plasma concentration of chloramphenicol was deter-
mined using high performance liquid chromatography coupled to
ultraviolet detection (HPLCeUV) and its lower limit of quantifica-
tion in human plasma was 100 ng/mL. Although HPLCeUV has
several advantages in terms of lower running cost, larger dynamic
range, and non-destructive detection, disadvantages include a
lower detection limit and a lack of structure-specific detection. This
earlier report did not quantitatively determine the transfer of
chloramphenicol in circulating blood in pregnant women treated
with trans-vaginal chloramphenicol. In contrast, liquid chroma-
tography coupled to tandem mass spectrometry (LCeMS/MS) can
detect analytes structure-specifically and sensitively compared
with HPLCeUV.
Few previous reports have examined the quantitative transfer of
trans-vaginal chloramphenicol to the maternal general circulation
using LCeMS/MS. In the present study, we developed a highly
specific and sensitive method for determining the plasma con-
centration of chloramphenicol by an LCeMS/MS in humans. This
study evaluated the transfer of chloramphenicol to circulating
blood in pregnant women treated with trans-vaginal chloram-
phenicol, and we investigated the correlations with maternal
background and the health of neonatal infants.
2. Patients and methods
2.1. Ethics
The study was performed in accordance with the Declaration of
Helsinki and its amendments, and the protocol was approved by
the Ethics Committee of Hamamatsu University School of Medicine
(approval number, 25-324). The patients received information
about the scientific aim of the study and each patient provided
written informed consent.
2.2. Patients and study schedule
The present study was an observation study conducted at
Hamamatsu University Hospital. A total of 37 Japanese pregnant
women receiving chloramphenicol vaginal tablets (Clomy® Vaginal
Tablet, Daiichi Sankyo Pharmaceutical Co., Ltd, Tokyo, Japan) for
bacterial vaginosis and its suspected case were enrolled. Bacterial
vaginosis was assessed by vaginal secretion characteristics ac-
cording to WHO diagnostic criteria. Each patient received 100 mg
chloramphenicol once daily trans-vaginally. Exclusion criteria were
as follows: patients (1) in whom obtaining the blood on schedule
for pharmacokinetic analysis was difficult; (2) who were being co-
treated with a drug metabolizing enzyme modifier; (3) with
impaired renal function (serum creatinine > 2.0 mg/dL); and (4)
with hepatic dysfunction (total bilirubin > 2.0 mg/dL). Blood sam-
ples were obtained on day 2 or later after starting the medication. A
Please cite this article in press as: Harauchi S, et al., Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its
relationship with their maternal background and neonatal health, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.03.015
2-mL blood specimen was withdrawn into tubes containing EDTA
dipotassium salts at 24 h post-dose. A second plasma specimen was
obtained from some patients after the first blood sampling. This
study is registered in the University Hospital Medical Information
Network (UMIN-CTR UMIN000021034).
2.3. Materials and solutions
Chloramphenicol was purchased from Wako Pure Chemicals
(Osaka, Japan). Chloramphenicol-d5 as an internal standard (IS) was
obtained from Sigma Aldrich (St. Louis, MO, USA). All other reagents
were of analytical grade and commercially available. Stock solutions
of chloramphenicol and IS were prepared with methanol. Standard
solutions of chloramphenicol were obtained by the dilution of a
stock solution with methanol. Calibration standards were prepared
in drug-free pooled plasma (Kohjin-Bio Co., Ltd, Sakado, Japan).
2.4. Plasma preparation for chloramphenicol measurement
Plasma was separated by centrifugation of the EDTA-treated
blood samples at 1670  g at 4  C for 10 min. For sample depro-
teinization, to 200 mL of plasma, 100 mL of IS solution (10 ng/mL) and
1000 mL of methanol were added into a microtube. After vortexing,
the mixture was then sonicated and cooled. Then the mixture was
vortex-mixed and centrifuged at 17,900  g, and the supernatant
was evaporated to dryness. The residue was reconstituted with
120 mL of mobile phase and centrifuged at 17,900  g. The super-
natant was injected into the LC system.
2.5. Determination of plasma chloramphenicol
Chloramphenicol in human plasma was determined using an LC
system (UFLCXR, Shimadzu Corporation, Kyoto, Japan) coupled to a
triple quadrupole mass spectrometer (3200 QTRAP®, AB Sciex,
Foster City, CA, USA) with an electrospray probe. Separation was
performed using TSKgel ODS-100V (particle size 3 mm, 2.0 mm
I.D.  75 mm, Tosoh, Tokyo). The mobile phase consisted of 20%
acetonitrile containing 5 mM ammonium acetate (pH 3.5), and the
flow rate was 0.2 mL/min. Chloramphenicol and IS were monitored
by the respective transitions of m/z 320.7e151.9 and 325.8e156.8
with collision energy levels of 20 eV, respectively. The linearity of
chloramphenicol was observed at concentration ranges of
0.1e100 ng/mL. The intra- and inter-assay accuracies of chloram-
phenicol were 100.5e107.1% and 100.7e106.0%, respectively. The
intra- and inter-assay precisions of chloramphenicol were
1.39e4.98% and 3.99e8.78%, respectively. The lower limit of quan-
tification for chloramphenicol in human plasma was 100 pg/mL.
2.6. Factors related to plasma chloramphenicol
This study investigated the quantitative transfer of chloram-
phenicol to the maternal general circulation and assessed the re-
lationships between the maternal plasma concentration of
chloramphenicol and maternal background. The parameters of
maternal background included the number of previous births,
gestational age at the first dosing, and clinical laboratory data. The
clinical laboratory data consisted of aspartate aminotransaminase
(AST) and alanine aminotransaminase (ALT) as hepatic dysfunction,
serum creatinine as renal function, C-reactive protein (CRP) and
white blood cell count (WBC) as inflammatory markers, and serum
albumin. To assess the influence of chloramphenicol treatment on
neonatal infants, the relationships between the maternal plasma
concentration of chloramphenicol and birth-weight, Apgar score at
birth, and the gestational age at the time of childbearing were
investigated.
 S. Harauchi et al. / J Infect Chemother xxx (2017) 1e6 3

2.7. Statistical analysis
All statistical analyses were performed using IBM SPSS 22.0J
Statistics (IBM Japan Ltd, Tokyo). The relationship between the
maternal plasma concentration of chloramphenicol and the factors
except for the birth experience and condition classification of
neonatal infants by Apgar score was analyzed using Pearson's test.
The number of previous births and condition classification of
neonatal infants by the Apgar score were analyzed using the
ManneWhitney U test. All values are expressed as the median and
interquartile range (IQR) unless otherwise stated. A P < 0.05 was
considered to indicate statistical significance.
3. Results
3.1. Maternal characteristics
Table 1 shows the maternal characteristics of the study popu-
lation. All patients enrolled were pregnant women with bacterial
vaginosis and were being co-treated with urinastatin vaginal sup-
pository. The medians of the maternal and gestational ages at
Table 1
Maternal backgrounds.
Maternal parameters Values
dosing were 31 years (IQR, 28e36 years) and 30 weeks and 3 days,
respectively. The subjects did not receive any medications other
than chloramphenicol and urinastatin.
3.2. Maternal plasma concentration of chloramphenicol
Fig. 1A shows the plasma concentration of chloramphenicol in
the subjects. The chloramphenicol concentration ranged from
0.043 to 73.1 ng/mL. Chloramphenicol was detected from all plasma
specimens. The median plasma concentration of chloramphenicol
was 10.1 ng/mL (IQR, 4.06e18.0 ng/mL) at the first sampling. The
median and IQR of the dose-normalized plasma concentration of
chloramphenicol were 5.71 and 2.34e8.85 ng/mL per mg/kg,
respectively. Fig. 1B shows the plasma concentration of the
chloramphenicol-administration day profile at the first sampling.
The median administration day was 7 days (IQR, 7e7 days). The
median days of the first and second sampling were day 3 (IQR, day
2e4) and day 7 (day 4e7), respectively. The maternal plasma
concentration of chloramphenicol declined significantly with the
administration day. The plasma concentration of chloramphenicol
was significantly lower at the second than the first sampling
(P ¼ 0.009).
3.3. Maternal backgrounds and clinical laboratory data

Age (years) 31 (28e36) The maternal plasma concentration of chloramphenicol was not
Body weight (kg) 54.4 (49.3e63.0) significantly correlated with maternal age (R2 < 0.001, P ¼ 0.94),
Body height (cm) 158 (154e162)
Primipara/multipara 18/19
number of previous births (P ¼ 0.36), or gestational age (R2 ¼ 0.16,
Total administration period (days) 7 (7e7) P ¼ 0.13). There was no correlation between body weight
Gestational ages at dosing (w.d) 30w.3d (24w.2de32w.5d) (R2 ¼ 0.040, P ¼ 0.24) or height (R2 ¼ 0.012, P ¼ 0.52) and the
Aspartate aminotransaminase (U/L) 15 (13e21) maternal plasma concentration of chloramphenicol. No significant
Alanine aminotransferase (U/L) 10 (7e18)
correlation was observed between the maternal plasma concen-
Serum creatinine (mg/dL) 0.43 (0.40e0.46)
Serum albumin (g/dL) 2.9 (2.8e3.3) tration of chloramphenicol and clinical laboratory data that
C-reactive protein (mg/dL) 0.27 (0.12e0.74) included AST (R2 ¼ 0.042, P ¼ 0.23), ALT (R2 ¼ 0.068, P ¼ 0.12),
White blood cell count (mL) 8220 (7180e9710) serum creatinine (R2 ¼ 0.003, P ¼ 0.77), and serum albumin
Data are expressed as the median and interquartile range in parentheses. The (R2 ¼ 0.13, P ¼ 0.68). The medians of CRP and WBC in patients at
clinical laboratory data were obtained at the first blood sampling. first sampling were 0.27 mg/dL (IQR, 0.12e0.74 mg/dL) and 8220/mL

Fig. 1. Maternal plasma concentration of chloramphenicol (A) and its relationship with administration period of trans-vaginal chloramphenicol at first blood sampling (B, n ¼ 37),
and multiple blood sampling (C, n ¼ 10). Box plots represent the median (bold line), 25th, and 75th percentiles, and the whiskers indicate the range and extend within 1.5 times the
length of the inner quartiles.

Please cite this article in press as: Harauchi S, et al., Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its
relationship with their maternal background and neonatal health, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.03.015
4 S. Harauchi et al. / J Infect Chemother xxx (2017) 1e6
(7180e9710/mL), respectively. No significant correlations were
observed between the plasma concentration of chloramphenicol
and CRP and WBC (Fig. 2).
3.4. Neonatal health
The medians of birth weight and Apgar score at birth were
2312 g and 8, respectively (Table 2). No infants were diagnosed as
gray baby syndrome at birth. Significant associations were not
observed between the maternal plasma concentration of chlor-
amphenicol and birth weight (R2 ¼ 0.008, P ¼ 0.58) or Apgar score
(P ¼ 0.79) of the neonates. The gestational age at the time of
childbearing was not correlated with the maternal plasma con-
centration of chloramphenicol (R2 < 0.001, P ¼ 0.90).
4. Discussion
Vaginal tablets containing chloramphenicol or metronidazole
are commonly used for the treatment of bacterial vaginosis in
pregnant women [12,13]. Chloramphenicol for bacterial vaginosis
easily passes through placenta and potentially has an effect on
neonatal infants. This study investigated the plasma concentration
of chloramphenicol in pregnant women treated with trans-vaginal
tablets and its relationships with maternal background and the
health of their neonatal infants at birth. In the present study,
plasma chloramphenicol was detected at the range of
0.043e73.1 ng/mL and there was a large variation in its concen-
tration. The maternal plasma concentration of chloramphenicol
decreased over time after first dose. No correlations were observed
between the maternal plasma concentration of chloramphenicol
and the maternal background or neonatal health at birth. These
findings suggest that there is a large variation in the uptake of
trans-vaginal chloramphenicol into the general circulation. To the
best of our knowledge, this is the first report to determine quan-
titatively the transfer of chloramphenicol to circulating blood in
pregnant women treated with trans-vaginal tablets.
Fig. 2. Relationship between maternal plasma concentration of chloramphenicol and clinical laboratory data. (A) White blood cell count and (B) C-reactive protein.
Please cite this article in press as: Harauchi S, et al., Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its
relationship with their maternal background and neonatal health, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.03.015
Table 2
Neonatal health parameters.
Parameter Value
Gestational age at birth (w.d) 36w.2d (34w.1de38w.4d)
Body weight at birth (g) 2312 (1954e2846)
Apgar score at 1 min after birth 8 (7e9)
6 points and less: asphyxia (n ¼ 9) 4 (3e5)
7 points and over: healthy (n ¼ 29) 8 (8e9)
Data are expressed as the median and interquartile range in parentheses (n ¼ 38).
Four pregnant women were not assessed because of patient transfer and stillbirth.
Five postpartum women had twins.
Chloramphenicol was detected from all plasma specimens of
the women in this study. Our LCeMS/MS method has a 1000-fold
sensitivity compared with an earlier study using HPLCeUV [5].
Our data indicate that vaginal chloramphenicol transfers to
circulating blood in pregnant women. In addition, the maternal
plasma concentration of chloramphenicol showed a large varia-
tion (IQR, 4.06e18.0 ng/mL). The maternal plasma concentration
of chloramphenicol in this study population was much lower than
the therapeutic range of chloramphenicol (5e20 mg/mL) in
typhoid fever [14]. Oral chloramphenicol is metabolized to the
glucuronate conjugate in the liver. Approximately 90% of the drug
excreted in the urine was reported to be in the form of glucuro-
nide [15]. The chloramphenicol clearance in humans was found to
be dependent on both renal and liver function, and renal and liver
function potentially cause the interindividual variability in the
plasma concentration of chloramphenicol [14]. No patient
enrolled in this study had kidney or liver dysfunction, and none
were receiving any medications that are known to have an effect
on chloramphenicol pharmacokinetics. These data indicate that
the clinical condition of bacterial vaginosis and pregnancy itself
potentially affects the variability of the maternal plasma con-
centration of chloramphenicol.
The plasma concentration of chloramphenicol declined with the
number of administration. In 10 patients with multiple blood
samplings, the maternal plasma concentration of chloramphenicol
 S. Harauchi et al. / J Infect Chemother xxx (2017) 1e6
was significantly lower at the second than the first sampling.
Generally, improvement of the inflammatory condition of the gut
mucous membrane reduces drug absorption [16]. The trans-vaginal
absorption of chloramphenicol through the vaginal mucous
membrane may also be increased by the inflammation caused by
bacterial vaginosis. Our data suggest that normalization of the self-
defense function in the vaginal mucous membrane after the
treatment of vaginal chloramphenicol decreases the maternal
plasma concentration of chloramphenicol in pregnant women.
The gestational age in this study population ranged from 16 to
36 weeks, classified as the second and early third trimester. In the
late second trimester, cardiac output and renal blood flow increase,
while hepatic blood flow does not change [17]. There were slight
differences in the gestational age and serum creatinine levels in this
study population. These data suggest the gestational age and
changes in renal function during pregnancy do not strongly affect
the individual variation in the maternal plasma concentration of
chloramphenicol. The parameters maternal background including
maternal age, number of previous births, and gestational age did
not influence the plasma concentration of chloramphenicol. In
addition, physical characteristics such as body weight and height
related to drug distribution were not associated with the plasma
concentration of chloramphenicol. These results indicate that the
physiological alterations during pregnancy are not responsible for
the interindividual variation in the maternal plasma concentration
of chloramphenicol.
No association between the maternal concentration of chlor-
amphenicol and inflammation markers such as CRP and WBC was
observed in the present study. These inflammation markers may
not reflect the condition of local inflammation caused by bacterial
vaginosis [18e20]. Mild bacterial vaginosis and its suspected case
have not been routinely graded using the clinical parameters
including inspection in clinical settings. The clinical parameters
would confirm that the absorption of chloramphenicol through
vaginal mucous membrane is affected by the degree of the
inflammation level and the cervical lesions. The trans-vaginal
chloramphenicol is administrated to pregnant women in order to
prevent premature birth induced by the inflammation of bacterial
vaginosis. In four women, the flora color of vagina secretions
changed from yellow or pinkish to colorless or white and the vol-
ume decreased in the present study. Changes in the color and
volume may indicate an improvement of the symptoms of bacterial
vaginosis by treatment of trans-vaginal chloramphenicol adminis-
tration. While CRP and WBC as clinical laboratory data are not
associated with an improvement of local vaginal inflammation, a
decline in the maternal plasma concentration of chloramphenicol
may be a useful as biomarker that reflects the improvement of
bacterial vaginosis.
The maternal plasma concentration of chloramphenicol was not
associated with neonatal health such as gestational age, body
weight, and Apgar score at birth. In reproduction test in rats,
300 mg/kg of chloramphenicol for 4 weeks was found to potentially
cause miscarriage and premature birth [21]. Chloramphenicol is
recognized as Class C in the United States FDA pregnancy category
[22]. In the present study, pregnant women with gestational ages
ranging from 16 to 36 weeks were exposed to by 100 mg of trans-
vaginal chloramphenicol per day for 7 days. However, those treated
with trans-vaginal tablets had much lower plasma concentrations
of chloramphenicol, compared with oral or intravenous adminis-
tration. In addition, our clinical study revealed that the maternal
plasma concentration of chloramphenicol did not affect the health
of the neonates at birth.
The present study has several limitations. First, the maternal
plasma specimens were collected just before administration of
trans-vaginal chloramphenicol. Also, we did not evaluate the
Please cite this article in press as: Harauchi S, et al., Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its
relationship with their maternal background and neonatal health, J Infect Chemother (2017), http://dx.doi.org/10.1016/j.jiac.2017.03.015
5
plasma concentration time-profile after medication. Chloram-
phenicol has a short half-life of 3e4 h [23] and a high concentration
is not maintained in human plasma. The maternal trans-vaginal
chloramphenicol level was considered to have little influence on
neonatal health at birth. Second, this study did not determine the
concentration of chloramphenicol in the umbilical cord blood.
Maternal chloramphenicol readily crosses the placenta [22]. How-
ever, the maternal plasma concentration of chloramphenicol after
trans-vaginal treatment was one one-thousandth that of the ther-
apeutic concentration in oral and intravenous treatments. The
umbilical cord blood concentration in this study is expected to be
lower than the therapeutic concentration. Third, pregnant women
with bacterial vaginosis were enrolled in this study. Trans-vaginal
chloramphenicol is also administrated to non-pregnant women.
Absorption of the drug through the vaginal mucous membrane in
non-pregnant women may not be identical to that in pregnant
women because pregnancy may affect the condition of the vaginal
mucous membrane [24,25]. The transfer of vaginal chloramphen-
icol to circulating blood in women who are not pregnant needs to
be clarified in further studies.
In the present study, the transfer of vaginal chloramphenicol
into the general circulation was quantitatively evaluated in preg-
nant women and the plasma concentration of chloramphenicol was
found to be in the range of 0.043e73.1 ng/mL. Based on the
quantitative transfer data of trans-vaginal chloramphenicol to
circulating blood, physicians can explain the administration of
trans-vaginal chloramphenicol to pregnant women from the
viewpoint of the risk-benefit balance. Our findings may be helpful
as safety information for the use of trans-vaginal chloramphenicol
in pregnant women.
In conclusion, this study established a highly specific and sen-
sitive method for determining the plasma concentration of chlor-
amphenicol using LCeMS/MS in humans. Vaginal chloramphenicol
transfers to circulating blood in pregnant women and we observed
a large variation in the maternal plasma concentration of chlor-
amphenicol that was correlated with the administration day, but
not maternal background or health of the neonate.
Conflict of interest
The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Acknowledgments
This work was supported by JSPS KAKENHI [grant number
15H00525].
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